PMID- 28580422
OWN - NLM
STAT- MEDLINE
DCOM- 20181010
LR  - 20181113
IS  - 2375-2548 (Electronic)
IS  - 2375-2548 (Linking)
VI  - 3
IP  - 5
DP  - 2017 May
TI  - HSP105 prevents depression-like behavior by increasing hippocampal brain-derived 
      neurotrophic factor levels in mice.
PG  - e1603014
LID - 10.1126/sciadv.1603014 [doi]
LID - e1603014
AB  - Heat shock proteins (HSPs) are stress-induced chaperones that are involved in 
      neurological disease. Although increasingly implicated in behavioral disorders, 
      the mechanisms of HSP action, and the relevant functional pathways, are still 
      unclear. We examined whether oral administration of geranylgeranylacetone (GGA), 
      a known HSP inducer, produced an antidepressant effect in a social defeat stress 
      model of depression in mice. We also investigated the possible molecular 
      mechanisms involved, particularly focusing on hippocampal neurogenesis and 
      neurotrophic factor expression. In stressed mice, hippocampal HSP105 expression 
      decreased. However, administration of GGA increased HSP105 expression and 
      improved depression-like behavior, induced hippocampal cell proliferation, and 
      elevated brain-derived neurotrophic factor (BDNF) levels in mouse hippocampus. 
      Co-treatment with GGA and the BDNF receptor inhibitor K252a suppressed the 
      antidepressant effects of GGA. HSP105 knockdown decreased BDNF mRNA levels in 
      HT22 hippocampal cell lines and hippocampal tissue and inhibited the GGA-mediated 
      antidepressant effect. These observations suggest that GGA administration is a 
      therapeutic candidate for depressive diseases by increasing hippocampal BDNF 
      levels via HSP105 expression.
FAU - Hashikawa, Naoya
AU  - Hashikawa N
AD  - Department of Life Science, Okayama University of Science, 1-1 Ridai-cho, 
      Kita-ku, Okayama, Japan.
FAU - Utaka, Yuta
AU  - Utaka Y
AD  - Department of Life Science, Okayama University of Science, 1-1 Ridai-cho, 
      Kita-ku, Okayama, Japan.
FAU - Ogawa, Takumi
AU  - Ogawa T
AD  - Department of Life Science, Okayama University of Science, 1-1 Ridai-cho, 
      Kita-ku, Okayama, Japan.
FAU - Tanoue, Ryo
AU  - Tanoue R
AD  - Department of Life Science, Okayama University of Science, 1-1 Ridai-cho, 
      Kita-ku, Okayama, Japan.
FAU - Morita, Yuna
AU  - Morita Y
AD  - Department of Life Science, Okayama University of Science, 1-1 Ridai-cho, 
      Kita-ku, Okayama, Japan.
FAU - Yamamoto, Sayumi
AU  - Yamamoto S
AD  - Department of Life Science, Okayama University of Science, 1-1 Ridai-cho, 
      Kita-ku, Okayama, Japan.
FAU - Yamaguchi, Satoru
AU  - Yamaguchi S
AD  - Department of Life Science, Okayama University of Science, 1-1 Ridai-cho, 
      Kita-ku, Okayama, Japan.
FAU - Kayano, Masafumi
AU  - Kayano M
AD  - Department of Emergency Pharmaceutical Sciences, Okayama University Graduate 
      School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, 
      Kita-ku, Okayama, Japan.
FAU - Zamami, Yoshito
AU  - Zamami Y
AD  - Department of Emergency Pharmaceutical Sciences, Okayama University Graduate 
      School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, 
      Kita-ku, Okayama, Japan.
AD  - Department of Clinical Pharmacy, Institute of Biomedical Sciences, Tokushima 
      University Graduate School, 2-50-1 Kuramoto-cho, Tokushima, Japan.
FAU - Hashikawa-Hobara, Narumi
AU  - Hashikawa-Hobara N
AD  - Department of Life Science, Okayama University of Science, 1-1 Ridai-cho, 
      Kita-ku, Okayama, Japan.
LA  - eng
PT  - Journal Article
DEP - 20170531
PL  - United States
TA  - Sci Adv
JT  - Science advances
JID - 101653440
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Carbazoles)
RN  - 0 (Diterpenes)
RN  - 0 (HSP110 Heat-Shock Proteins)
RN  - 0 (Hsp105 protein, mouse)
RN  - 0 (Indole Alkaloids)
RN  - 97161-97-2 (staurosporine aglycone)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - S8S8451A4O (geranylgeranylacetone)
SB  - IM
MH  - Animals
MH  - *Behavior, Animal
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Carbazoles/pharmacology
MH  - Cell Line
MH  - Depression/*metabolism/pathology
MH  - Diterpenes/pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - HSP110 Heat-Shock Proteins/*biosynthesis
MH  - Hippocampus/*metabolism/pathology
MH  - Indole Alkaloids/pharmacology
MH  - Male
MH  - Mice
MH  - Receptor, trkB/metabolism
MH  - Stress, Psychological/*metabolism/pathology
PMC - PMC5451194
EDAT- 2017/06/06 06:00
MHDA- 2018/10/12 06:00
PMCR- 2017/05/31
CRDT- 2017/06/06 06:00
PHST- 2016/11/30 00:00 [received]
PHST- 2017/04/07 00:00 [accepted]
PHST- 2017/06/06 06:00 [entrez]
PHST- 2017/06/06 06:00 [pubmed]
PHST- 2018/10/12 06:00 [medline]
PHST- 2017/05/31 00:00 [pmc-release]
AID - 1603014 [pii]
AID - 10.1126/sciadv.1603014 [doi]
PST - epublish
SO  - Sci Adv. 2017 May 31;3(5):e1603014. doi: 10.1126/sciadv.1603014. eCollection 2017 
      May.